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Thursday 13 December 2018

Low Level Laser Therapy (LLLT) for Autism – seems to work in Havana


Today’s post is all about one of the potential medical, but non-drug, interventions for autism. The others tend to involve electrical/magnetic stimulation of one kind or another.
Low level laser therapy (LLLT) was developed more than fifty years ago in Russia. Today in Western countries LLLT is often regarded as alternative medicine or just quackery.  There are some FDA approved devices.  In Russia and some East European countries LLLT is part of mainstream medicine.
Two people forwarded me a recent study that was carried out in Havana by a team from Cuba and Israel.
There are only 11 million Cubans, but there are a lot of Cuban doctors.  They have developed interesting drugs, some related to cancer, that are now being taken up by Western medicine.  Cuba actually leases out doctors to work in more than 50 developing countries around the world.
The results of the study are indeed interesting and there is a long list of possible mechanisms that may be involved.
The question we are left with is can you achieve a similar result with cheap LEDs (light emitting diodes), or do you need a genuine laser (that confusingly use a different kind of diode).  I do not know the answer, but there is definitely a difference.  

Let’s start with the background to LLLT

 In Russia (formerly USSR) study of biomodulation action (BMA) mechanisms of low-intensity laser irradiation (LILI) began in 1964, immediately after the development of lasers. During the period from 1965 to 1972 several dozens of scientific conferences were held, hundreds of studies were published. Generally, secondary mechanisms and results of LILI effect on patients with various diseases were studied. This data was immediately implemented into practical medicine in the fields of oncology, surgery, dermatology and dentistry, and since 1974 low level laser therapy (LLLT) is included in the standard of state medical care. For 50 years no less than 1000 books were published (monographs, collections, methodical and clinical materials), thousands of researches were carried out. Primary mechanism and patterns of interaction of LILI with acceptors within cells can be represented in the following order: absorption of photon’s energy – emergence of a local temperature gradient – release of Ca2+ from intracellular stores – stimulating Ca2+–dependent processes. Understanding of this process allowed the explanation of all known secondary effects, optimized methods and extremely increased effectiveness of LLLT. Owing to the knowledge of BMA mechanisms of LILI, numerous associated and combined LLLT techniques were developed and are widely used nowadays: locally, on the projection of internal organs, laser acupuncture, reflexology, intracavitary, transdermal and intravenous laser blood illumination, magnetic-laser therapy, laser phoresis, laser-vacuum massage, biomodulation, etc. About 400 000 laser therapeutic devices are used in Russian practical healthcare. Unique, having no analogues in the world devices, are produced – red pulsed laser diodes (wavelength 635 nm, power 5-40 W, pulse duration 100 ns, frequency 10 000 Hz) are designed specially for effective laser therapy. 

About 400 000 laser therapeutic devices are used in Russian practical healthcare; about half of them are used in professional medicine (clinics), and half of them – at patients’ home for independent use. Around the world only lasers designed for other purposes (technical) are used, which are not always effective in medicine. The peculiarity of Russian laser therapeutic apparatus is the development and production of special lasers, designed specifically for therapy. For example, unique, having no analogues in the world, devices are produced - red pulsed laser diodes (wavelength 635 nm, power 5-40 W, pulse duration 100 ns, frequency 10 000 Hz) are designed specially for effective laser therapy.
Laser therapy is widely used in almost all medicine fields: obstetrics and gynecology, gastroenterology, cardiology, dermatology and cosmetology, neurology, oncology, otolaryngology, pediatrics, pulmonology, dentistry, traumatology and orthopedics (diseases of musculoskeletal system), urology and andrology, phthisiology, etc. 

Cheap LEDS vs Expensive Lasers? This paper says you cannot cut corners.

The question of lasers' exclusivity, as well as the degree of influence of special properties of low-intensity laser illumination (LILI), such as coherence, polarity and monochromaticity, on the effectiveness of low level laser therapy (LLLT) continues to cause arguments.
The study analyzes publications from 1973 to 2016, in which laser and conventional light sources are compared, and the following conclusions are drawn. First, there are a lot of publications with incorrect comparison or unfounded statements. Secondly, other sources of light are often meant by LILI without any justification. Thirdly, all studies, in which the comparison is carried out correctly and close parameters of the impact and the model are used, have a firm conclusion that laser light is much more effective. Fourthly, it is uniquely identified that the most important parameter that determines the efficiency of lasers is monochromaticity, i.e., a much narrower spectral width than for all other light sources.

Only laser light sources can be used for LLLT! 


Here is the Cuban study on autism using lasers:-


The study examined the efficacy of low-level laser therapy, a form of photobiomodulation, for the treatment of irritability associated with autistic spectrum disorder in children and adolescents aged 5–17 years. Twenty-one of the 40 participants received eight 5-min procedures administered to the base of the skull and temporal areas across a 4-week period (test, i.e., active treatment participants). All the participants were evaluated with the Aberrant Behavior Checklist (ABC), with the global scale and five subscales (irritability/agitation, lethargy/social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech), and the Clinical Global Impressions (CGI) Scale including a severity of-illness scale (CGI-S) and a global improvement/change scale (CGI-C). The evaluation took place at baseline, week 2 (interim), week 4 (endpoint), and week 8 (postprocedure) of the study. The adjusted mean difference in the baseline to study endpoint change in the ABC irritability subscale score between test and placebo participants was _15.17 in favor of the test procedure group. ANCOVA analysis found this difference to be statistically significant (F ¼ 99.34, p < 0.0001) compared to the baseline ABC irritability subscale score. The study found that low-level laser therapy could be an effective tool for reducing irritability and other symptoms and behaviors associated with the autistic spectrum disorder in children and adolescents, with positive changes maintained and augmented over time. 

A pulsed laser of 635 nm with a power output of 15 mW and a red 635 nm LED were used as treatment and placebo, respectively.

 A significant literature exists on the ability of low-level light therapy (LLLT) to penetrate the skull. Low-energy light passes the skull and a therapeutic effect likely exists. LLLT systems employ the so-called quantum optically induced transparency effect. This effect controls optical properties of dense media enhancing transparency contrast by a factor of five. Therefore, the skull, spine, or joints can be penetrated even with moderate intensity light reaching deep layers in muscles, connective tissue, and even bone, enabling transcranial effects of LLLT.
LLLT achieves a therapeutic effect by employing non-ionizing light, including lasers, light-emitting diodes, or broadband light in the visible red (600–700 nm) and near-infrared (780–1100 nm) spectra. LLLT is a nonthermal process occurring when a chromophore is exposed to a suitable wavelength of light. Chromophores are responsible for the color associated with biological compounds such as hemoglobin and cytochromes. With chromophore absorption of a photon of light, an electron transits to an excited state, with a physiologic effect occurring when photons dissociate the inhibitory signaling molecule nitric oxide (NO) from cytochrome-C-oxidase, increasing the electron transport, mitochondrial membrane potentials, and production of mitochondrial products such as ATP and NADH. Other effects include the production of reactive oxygen species (ROS) which activate transcription factors, leading to the cellular proliferation and migration.

Based on these complex characteristics, LLLT possesses physiologically modifying properties associated with light characteristics such as wavelength and irradiance, varied by exposure parameters, such as energy density, irradiation duration, and treatment frequency. On the basis of the above, we investigated behavioral and cognitive changes in ASD as a consequence of the delivery of red LLLT.


2.4 Procedure
All the 40 participants completed the course according to the protocol. Twenty-one of them were randomized to the test (active treatment) procedure group, and 19 were randomized to the placebo procedure group. Participants received eight 5-min laser light applications to the base of the skull and temporal areas with the Erchonia® EAL Laser (active or sham) across a 4-week period: two applications per week, 3–4 days apart at the investigator’s test site.A pulsed laser of 635 nm with a power output of 15 mW and a red 635 nm LED were used as treatment and placebo, respectively. Participants were required to maintain their regular medication schedule and treatment regimens, as reported at the baseline evaluation, to treat symptoms related to autistic disorder throughout the study time. All of them complied with this requirement.  

Twenty out of the 21 active treatment participants showed some degree of improvement in autism-related symptoms at endpoint relative to baseline. The majority (13) received ratings of “much improved”. No placebo group participant demonstrated improvement in symptoms at endpoint relative to baseline. The majority (17) demonstrated “no change”, and the remaining 2 placebo participants rated “minimally worse”. We found that the ABC global and five subscale scores decreased progressively and significantly from baseline across each of the three successive evaluation points; the decrease progressed over time, including a 4-week followup during which no further LLLT occurred. Conversely, the placebo group demonstrated no significant change across the study duration, demonstrating the effectiveness of LLLT in reducing ASD-associated symptoms.





Conclusion 
Either the researchers have cheated, which has been known to happen, or Low Level Laser Therapy (LLLT) is indeed a worthwhile therapy for much autism.  The question of safety should be carefully considered.

Judging by the drugs the participants had been taking, they were not kids with trivial autism.


According to the current FDA standards, an FDA cleared LLLT device (also called a cold laser) can be sold for 3 main issues: 
·        Pain Control

·        Inflammation Reduction

·        Increased Blood Flow  

The cheapest FDA approved laser device that would be vaguely equivalent to the device used in the trial in Cuba costs $2500 in the US.
Hopefully, one day someone will compare the effect on subjects with autism of cheap LED devices versus true laser devices.




This press release was highlighted by our reader RD:-



Erchonia Submits Data to US FDA to Support Low-Level Laser 510(k) Market Clearance for Autism
Quadruple-Blind laser study proves success in treating Autism in children and adolescents.
“The results are so strong, nobody can argue them.”

MELBOURNE, Fla. (PRWEB)September 05, 2018
Erchonia, the World Leader in Low Level Laser technology, announces today that they have submitted data to the US FDA to support a 510(k) market clearance for Autism.
The clinical trial was a quadruple-blind (Participant, Care Provider, Investigator and Outcome Assessor), randomized, placebo-controlled, and crossover clinical trial. The study was designed to treat autistic children with the 640nm Erchonia Spectrum Laser as the active device or a 640nm LED or light emitting diode as a placebo device, which had the same power output. FDA input was obtained prior to clinical trial and implemented into the protocol.
Both test and placebo patients were treated twice a week for 4 weeks. Post-treatment follow-up on both sets of patients was performed after 4 weeks, 8 weeks, and 6 months. At the end of 6 months, patients from the LED placebo group were crossed over and then given Erchonia’s Spectrum Laser treatment protocol. The results were documented and submitted to the US FDA for a 510(k) market clearance De Novo Application.
The inclusion criteria consisted of autistic children between the ages of 5 to 17 years old, and progress was measured by using the ABC or Aberrant Behavior Checklist as the primary diagnosis. The ABC 58-point symptom checklist was used to assess and classify behaviors of irritability and agitation; lethargy and social withdrawal, stereotypic behavior, hyperactivity and noncompliance, and inappropriate speech in children with developmental disorders. The ABC tests were performed at baseline, 2 weeks, and 4 weeks during the treatments phase, and 4 weeks, 8 weeks, and 6 months post-treatment in both the treated and placebo groups.
“This is a well-designed trial that shows evidence supporting the use of Low Level Laser Therapy in children and adolescents with autism,” said Dr. Morales-Quezada, Associate Research Director at Spaulding-Labushagne Neuromodulation Center. “Moreover, the technique proved to be safe and well tolerated by the study participants. The active intervention showed to be more effective than the placebo (sham) device in treating symptoms of autistic disorder, and this statistically significant treatment effect was observed for all clinical outcomes, by the end of the intervention period and after the 6 months follow-up. This evidence offers a new treatment option to be considered for children and adolescents with autism.”
Calixto Machado, MD, PhD, FAAN, President of the Cuban Society of the Clinical Neurophysiology Institute of Neurology and Neurosurgery agreed, “Results are so strong, nobody can argue them.”
Steven Shanks, President of Erchonia stated, “This study from a scientific perspective is one of the most stringent ways to perform a clinical trial. The original placebo patients have now acted as their own control group. The LED that was used as a placebo showed no results even though we used the same wavelength and power output.”
The Erchonia Spectrum Laser implemented in this clinical trial was a prototype laser and is not currently sold. While waiting for the 510(k) market clearance, Erchonia will start the development process for the new Erchonia Spectrum Laser.
Erchonia would like to thank Calixto Machado, MD, PhD, FAAN, Mauricio Chinchilla, MD, Yanin Ferrer, MD, and the University of Havana for their dedication to research and helping Erchonia with its latest achievement.
About Erchonia. Erchonia created the low-level laser category in January 2002 when the FDA granted Erchonia the very 1st 510(k) market clearance for any low-level laser. This new study further sets Erchonia apart from its competitors based on their commitment to research and numerous 510(k) market clearances obtained through blind and controlled clinical trials.




43 comments:

  1. LLLT works through hormesis, it actually induces oxidative stress. This is why I think it is ever more important to use exactly as a research setting would. Here is one such example:

    Biphasic Dose Response in Low Level Light Therapy
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790317/

    While I havent researched if LLLT can actually increase things such as NRF2 and other antioxidant pathways it would make sense.

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    1. Aspie, thankfully in the autism study above they published the technical details of therapy, so it can be replicated quite easily if you have a medical LLLT device.

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    2. Thats great and an absolute must especially when dealing with neuro impairments (so to speak) such as autism which clearly has an oxidative stress factor.

      Also it would be interesting to hear from people on here if they experimented with LLLT home devices (the cheaper ones) what their results were.

      My knowledge on LLLT is extremely limited btw, I have done some reading on it and from my understanding the benefits are due to the induction of ROS (very small amount and enough to induce a hormetic effect).

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    3. I did not experiment with it at home, but at a place called Terrasuit in my country which also does Masgutova reflex integration. My then 3 year old with serious hyperactivity problems would sit down for an hour for it without any problems and actually push her arms and legs towards the laser as they were using it on different points. I have decided to buy one next year (it takes some time to learn how to use it and I have too much to handle right now) and I will let you know. The one I wil buy - QRI laser - costs about 2500 usd.

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  2. Aspie, I left a comment for you in the previous post, there I explain you my son's characteristics, I can say that at 5 mg memantine was like a psichodelic drug for him, definitely I did the wrong trial.
    Valentina

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  3. Whats the weight of your son valentina, as stated before Im 95kg (I think, I dont weigh myself that often and I find that body fat % and exercise capacity to be a better indicator for me).
    Anyway I found that 5mg allready was a high dose for me when starting it, especially the first 5-10 days, I could see why memantine has recreational/pro-euphoric qualities.

    Also I cant the find the post you made do you have a link? Ill read it.

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    1. Aspie, my son's weight is 38 kg, he has mitochondrial dysfunction(hypotonia,dismotility and constipation). On the other hand, he has manias, some tics and rituals. Lately he is having extreme anxiety, he needs to grab any object, he joins and hide them. He is cheerful and sociable with his friends and loves going to his grandmother's house to play, study history and ask her to tell him stories from the past. He wants kisses from me or his father. But he has all kinds of fears.
      Valentina

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    2. Valentina, I would not dare to give you advice on dosing (sorry). But I would like to add that looking back to my own youth I do find myself in the behavior of ritualistic behavior for example: putting my pants proper and lifting them so to speak literally 100 times per day, watching the same movie over and over 10 times per week.
      Constipation my body always also tends to want to go to, magnesium citrate (low doses) can normalize stool pretty efficiently (only needs about 100-300mg worth).
      Hypotonia I never really had personally. I had clumpsy motor planning and problems with fine motor skills (dopamine controls fine motor skills) and the cerebellum is very important in motor planning.
      Alpha gpc did wonders, but the gut nausea, crazy white heads (acne) were unacceptable so I discontinued that.
      Interestingly alpha gpc (but not cdp-choline or any other 'raw' choline building block so to speak) powerfully changes serotonin/dopamine balance in 3 important areas implicated in autism: cerebellum, striatum and also frontal cortex.
      Ill try find the study later if your interested but alpha gpc is not some hippy like supplement btw, it actually got banned here in europe last year and its not allowed to be imported anymore, showing that it can have potent effects in some.

      Regarding fears and anxiety, I also had them as a kid, fear of death, insecurities regarding going school every day. Interestingly, after the chemical cocktails I had during puberty (lots of ssris and antipsychotics) my apathy increased steadily (also upon discontinueing of the drugs), I became more socially withdrawn, but strikingly the shift in the type of 'repetitive behavior/tics' became very noticeable, I became less anxious in presence of others (due to apathy and indifference, which is very bad imo).

      Anxiety and fears can have multiple origins (in my opinion). It is hard but worthwhile figuring out where the problem comes from as the wrong drugs can sometimes even have lasting side effects (im a living example of this).

      Dopamine can be both anxiolytic and anxiogenic, depending on the individual and their natural balance between all the neurotransmitters. In fact both low dopamine and high dopamine can make one anxious. Also I believe that properly targetting fears is most efficiently done through modulating fear acquisition AND fear extinction (drugs that increase extinction and dont touch acquisition that much are the safest bet). Keep in mind that you need some form of fear acquisition/recognition. In fact im confinced that people learn and are motivated due to the fact that are able to sense fear, think about it, if you have no fears or do not perceive fear in dangerous situation. Motivation is just a byproduct of survival mechanisms, healthy motivation (keep going to your job to earn money) is necesarry to make sure you can buy those extra warm sheets for the winter, buys you that extra locker on the door after you have heard that recently a burgerly has taken place in your neighborhood.

      You dont want to simply block fear acquisition to give someone relieve, what you can get then is extremely reckless behavior and sensation seeking, as the sense of fear is part of learning behavior and can release dopamine. Blocking fear acquisition could make a kid naive for example and if some dirty friggin pedofile would pick out that vulnerable kid, well the naive kid would be less likely to say no to go with him. Once again I would like to highlight that having some form of fears if healthy and needed, however when fears start taking over daily life then some consideration has to be taken to target these systems with powerfull drugs.

      From what I understand you have your son on valproic acid? As far as I know vpa is also a hdac-i? I do know that most hdac-i's such as butyrate, sulforaphane and possibly also vpa? enhance fear extinguishment, this could also be the reason why your son does so well according to you on it.

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    3. Now memantine is a nmda blocker (this would alter fear perception pathways considering nmda its important role in fear processing)
      My own experience is that it did make me more outgoing and I had far less repetitive behavior on it, also less worrying while at work, I can imagine however that it makes certain kids more impulsive (once again it will highly depend on the individual)

      Just googled it for you and yep memantine does have an effect on fear processing:

      Hippocampal neurogenesis enhancers promote forgetting of remote fear memory after hippocampal reactivation by retrieval
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5036964/

      '-->> Forgetting of recent fear memory is promoted by treatment with memantine (MEM) <<--, which increases hippocampal neurogenesis. The approaches for treatment of post-traumatic stress disorder (PTSD) using rodent models have focused on the extinction and reconsolidation of recent, but not remote, memories. '

      What I understand from this is the type of fears that your son would experience at school, could be relieved by memantine. However other fears? I wouldnt dare to draw any conclusions on that.

      Also I suspect I might have mito dysfunction myself eventhough 23andme did not point towards it I do have low adiponectin and things such as taurine (which increase it) Ive always responded well to, also coq10 my body likes very much and sulforaphane.

      One last thing regarding memantine: it is important to understand (if you decide to try it) that the initial days nACHr is antagonized, this would be anti-cognitive, however these receptors upregulate pretty fast according to science and thats also part of the beneficial effect in alzheimer (which memantine is mainly used for). First few days on memantine were far more disinhibited and entertaining in a semi recreational way so to speak than when I was on it for 5+ days, it became more of a stable happy motivated state then. From what I understand it is sometimes even prescribed as a mood stabilizer aswell to certain people in psychiatry.

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    4. Thanks Aspie, your help is very valuable,everything you tell me about you. We stopped valproate a year ago, now we are on Zarontin an antiepileptic wich induces neurogenesis. I didn´t know that memantine enhances neurogenesis, rather the opposite.My son´s fear number one is to death.
      Valentina

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    5. Not a problem.

      Sounds like me as a kid Valentina, during this time of the year + winter I still have it sometimes. I will get my sunlamp (10.000lux) out of the closet soon as I know my hypochondriac symptoms always get bad this time of the year aswell.
      If its due to increase in serotonin or dopamine that brightlight helps me, im not sure it affects lots of things.

      Interesting study this I found today btw (someone posted it on reddit):

      How UV Light Touches the Brain and Endocrine System Through Skin, and Why.
      https://www.ncbi.nlm.nih.gov/pubmed/29546369/


      Memantine did help me with irrational fears, it made me feel so free in fact like as if I was on holiday... thinking back about last year while I was on it sometimes makes me tearfull (realising how I good I felt on it back then). Tearfull in a nostalgic way.

      Regarding your sons fears, I think its pretty save to assume that during darker days these fears aggrevate?

      Zarontin I just looked up I never heard of it seems a pretty serious drug, but its probably needed for his seizures?
      Memantine (not sure about potency in comparison to zarontin), does seem to have some anticonvulsant activity (which makes sense as it seems to be capable of blocking some type of calcium channels)

      Anticonvulsant effects of memantine and MK-801 in guinea pig hippocampal slices.
      https://www.ncbi.nlm.nih.gov/pubmed/7627576

      Once again Im very cautious, and wouldnt dare saying if it is effective with regards to this in humans at all. Also there are many types of calcium channels, L, T, N. From what Ive seen is that Zarontin is a T type blocker.

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    6. Hi Aspie,started memantine today, had to divide the 10 mg tablet into 6 parts of 1.6 mg, not very equal.I plan to start with this dose for 5 days and then keep 2.5mg that would be more accurate as it is a quarter tablet, easier to divide. The problem is that would be only one dose per day. He didn't laugh at bedtime as he was doing lately. Nice start!
      Valentina

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    7. Yep, the tablets I had were also a pain to cut, even the breaking line on the 10mg tablet it was actually to hard to properly make 5mg parts lol, let alone when I was doing the 7.5mg per day in the end, it was more like either 8.5mg one day and then with remaining little crumbles it was 6.9mg maybe the day after lol.

      Id recommend taking the dose atleast for 7 days before changing, memantine has an incredibly long halflife (around 70hours from what I remember). If you notice him getting hyperactive or mentally being 'somewhere else' too much, this is part of the dissociative effect memantine can have.
      I only had this really the first 3 days when I started on 5mg.
      I think if it works out for him (which I really hope) it can potentially really help him, since I found that it starts acting more as a mood stabilizer and antistress agent after 10-14 days in and onwards.

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    8. Thanks Aspie, I will keep the dose for 7 days and then stay in a quarter tablet if he respondes well.Will keep you posted.
      Valentina

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  4. Low level light therapy (using both red/infrared lasers and cheaper LEDs) is now more commonly known as photobiomodulation.

    Last year, I bought a Vielight 810 device for $500 USD and tried it on my autistic son for 8 weeks. I didn't see any improvement in cognition, hyperactivity or stimming.

    The 810 outputs 810nm infrared light from a LED diode built into a nasal insert (clip), so the light supposedly has better penetration through the skull and into the brain. Infrared light is supposed to have better penetration than red light so I'm surprised this trial used 635 nm.

    I just read a book called "Red Light Therapy" which says Michael Hamblin (a prominent photobiomodulation researcher) doesn't think the 810 can penetrate into the brain that well and he recommends using a more powerful Vielight device, which costs $2K USD and also uses LEDs. (Vielight hopes to treat dementia with their products.) Hamblin doesn't think lasers are more effective than LEDs- but he could be wrong, of course.

    There's lots of promising photobiomodulation research but too many unknowns, including the optimal dosage, which is critical since it has a bi-phasic response in which too high a dose renders the treatment ineffective. Hopefully, this study is real.

    RD

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    1. RD, thanks for your feedback.

      635nm is the standard wavelength for laser devices used in LLLT, I think that is why they used it. It also means it is easy to replicate this study using a wide variety of devices. The only constraint is your budget.

      You raised the same issue that Aspie1983 has in the paper he links to, that dose does matter. The bi-phasic response also applies to many drug therapies. Too much or too little may give no benefit.

      Personally, and not being an LLLT expert, I think different people are likely benefiting from entirely different biological mechanisms, just like we see with C8/BHB therapy. LLLT is used for so many different medical problems.

      Laser light is different to LED light because it is all at the same wavelength. With LED light the light is not "clean" and your 810 device really means the average wavelength is 810nm. To the extent that having just one wavelength of light matters, nobody seems to know. The laser people think it matters and the people selling LEDs say it does not.

      Hopefully some reader will replicate the study and let us know their results.

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    2. Here's a press link from Erchonia about this trial. They're a medical device manufacturer so they only sell to doctors.

      https://www.erchonia.com/erchonia-submits-data-to-us-fda-to-support-low-level-laser-510k-market-clearance-for-autism/

      Also, here's the link to the Vielight Neuro, which is recommended by Hamblin, for the brain:
      https://vielight.com/product/vielight-neuro-alpha/

      Also, to answer an earlier question: before trying the Vielight 810, I bought and tried a much cheaper, hand-held LED lamp (830 nm) on my son- but there was no benefit.

      RD

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    3. RD, very interesting and particularly that they explain that the placebo LED was not only the same wavelength but also the same power.

      So I think we can conclude that it has to be a laser.

      We I live physiotherapists use laser LLLT and I see that there are laser devices sold for home use in the US.

      Here is just one vendor.

      https://www.coldlasers.org/home-equipment/

      They are very expensive.

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    4. I did a 3 month trial of the Vielight Neuro on my 12-year old autistic son. I tried the Neuro first since it's much cheaper than a laser. Unfortunately, there was no improvement. (Thankfully, Vielight has an 80% refund policy.) I then tried the red laser treatment on my son. At this point, I consider him "improved" (but not the "much improved" or "very much improved" I was hoping for). Below is info for those who want to try it.

      Erchonia's autism patent.
      http://www.freepatentsonline.com/y2018/0169436.html

      Avant's overview of laser therapy.
      https://avantwellness.com/choosing-your-next-laser/

      Erchonia's defense of low power red laser therapy.
      https://www.erchonia.com/wp-content/uploads/2017/07/Maloney_Power-and-Penetration-Myth_01_08.pdf

      The Erchonia study says a pulsed 15mW red laser was applied on the temples (sides of the head) and the back of the head for 5 minutes twice a week for a total of 8 treatments. (I do it by walking constantly back and forth around my son while shining the laser several inches from his head in a sweeping, continuous motion.) Erchonia's patent says the lasers should be pulsed at 8/53/73 and 101 Hz. (LEDs can be pulsed as well but only lasers can be "super-pulsed".) Erchonia uses very low power but they claim the pulsing makes up for this and that higher power is not better (link #3).

      I bought an Avant LZ30-X laser for $5k USD because its specs are the closest to Erchonia's lasers. The cheaper -P does NOT have "advanced" programmable options. The LZ30 is controlled with "arrow" buttons:
      a. From the "Advanced" settings, enable the "Power" option (allows you to change the power level) and the "Custom" option (allows you to create your own pulsing protocols).
      b. You can then create+save a single custom protocol with pulsing at 8/53/73/101 Hz. The laser will automatically cycle through all 4 frequencies, switching to a different frequency every 3 s.
      c. When you turn on the laser, you can also lower the red power level from the default 250mW -> 15mW (by pressing the left arrow) and this setting is saved.

      Note: I had to call Avant to learn how to do a-c because the user manual has obsolete specs+info. Also, you and the "patient" MUST wear the provided "sunglasses" when the laser is on + NEVER look directly into the laser. Also, I recommend starting treatment after a crewcut since hair blocks light.

      After 3 weeks of treatment, I began to see improvements: most of my son's speech consists of impulsive, obsessive questions. Now, his speech has very noticeably improved and there's been a reduction in his obsessive thoughts/questions. His focus has also improved (he was able to tie his shoes by himself for the first time). Red laser therapy then may be the first treatment we've tried that actually helped. (We've tried many treatments over the past 6 years, including a 3 month trial of bumetanide.) However, I haven't noticed much cognitive improvement yet, which is a big disappointment. My son's autistic behavior is relatively mild but overall I consider him a moderate case because his IQ is only 50. He can read at a 2nd grade level but we've been trying to teach him how to understand time (clock, calendar, etc.) and basic math for years with little progress.

      I'm trying 1 below now and will possibly try 2-4:
      1. Continue treatment like before to see if there's further improvement.
      2. Focus on a different part of the head (forehead + top of the head) instead of the temples/back of the head.
      3. Increase the dosage by boosting the power level or treatment time. (Too high a dose, though, can back-fire.)
      4. Switch to high-power Infrared laser therapy (the LZ30-X supports 808nm@900mW max).

      RD

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    5. RD, thanks for your very comprehensive report on your low level laser therapy.

      I think the clinical trial does show that this is a serious non-drug therapy for autism. I am not convinced about some of the other expensive non-drug therapies, like neurofeedback.

      The precise method used will be very important and please keep us updated as you refine your method. Hopefully, Erchonia will also publish more information and conduct further trials.

      Regarding bumetanide, what dose did you use? One parent I know tried it five years ago with no result, but is now repeating at a higher dose and it is the improvement in math skills that has convinced him that there is a benefit. Also of interest is that while in the first trial there was diuresis, now there is very little, even at a high dose of 3mg. I do think that in some non-responders to bumetanide, the dosage used was too low.

      Delete
    6. Peter,
      Last year, we tried bumetanide (0.5 mg bid for 1 month and 1 mg bid for 2 months). During the trial, I felt there was some cognitive improvement (e.g. he got better at adding single digits) but after we stopped, there was no deterioration. We decided not to try it again because his appetite declined and he noticeably lost weight (he's already skinny). His appetite came back and he regained weight after we stopped.

      I should clarify that I consider my son's speaking/attention to be "much improved"- what he says makes much more sense now. However, so far there's been minimal cognitive improvement so overall, I consider him only "improved".

      Here are two additional links:
      These are slides from the trial's lead researcher. Page 24 shows the "helmet" from the Erchonia patent. Was this used for the trial instead of a hand-held laser? If so, the power was 5 lasers x 7.5mW= 37.5mW, not 2 lasers x 7.5mW= 15mW. Or perhaps the 5 lasers were alternately turned on (2 at a time)?
      https://www.researchgate.net/publication/324530892_Effects_of_Low_Level_Laser_Therapy_in_Autistic_Spectrum_Disorders_-_Part_2

      This is an article about using high-power infrared lasers for tramautic brain injury (TBI). This is the opposite approach to Erchonia.
      https://www.westword.com/news/colorado-doctors-using-lasers-as-a-weapon-against-tbi-other-brain-injuries-9223729

      Again-many thanks for your blog. I wouldn't have tried this on my own without it.

      RD

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    7. RD, since you have first hand experience, I think you might want to contact these researchers and open up a dialogue. I think they may well be happy to discuss practical issues with you.

      If such a method can deliver significant benefits, more people need to know about it.

      Delete
    8. Peter,
      I emailed Erchonia and one of the researchers months ago but didn't get a reply. (I'm not a customer or a doctor/scientist so there's no reason for them to reply to me.)

      I'm finishing up a 2nd round of 8 treatments now (I started laser therapy 2.5 months ago). Afterwards, I'll give my son a break before starting round #3- either increase the dosage or apply the laser to a different location on the head.

      RD

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    9. RD, well at least you tried to make contact.

      There is quite a lot of information on why this therapy may be effective and I will write another post shortly. There must be an optimal way to use this therapy and you are as likely to find it as the "experts", perhaps more likely.

      Delete
  5. AJ/Tyler, Not sure which one of you two digged into the whole milk and gut opioid thing, but I thought id share this with you:

    The impact of milk caseins on behavioural development in rats : exploring the role of the gut brain axis.
    http://epubs.surrey.ac.uk/846301/

    "Exposure to milk caseins beyond the normal weaning age in rats (21 days) was shown to impact the development of the opioid system, a key player in emotional regulation. Further, milk alters the gut microbiome and evidence suggests the gut microbiota can modify brain function and behaviour. Given such evidence, it is hypothesised exposure to milk casein and its bioactive breakdown product, beta casomorphin-7 (BCM-7) beyond weaning age in rats results in disruptions to brain neurochemistry and behaviour via a microbiome-gut-brain axis mechanism. This work aimed to investigate this hypothesis using in vivo behavioural, neurochemical, gut microbial and metabonomic studies. The behavioural results showed that exposure to casein from postnatal day 21-26 resulted in an increase in ‘depressive-like’ behaviour as measured by the forced swim test (FST) and that BCM-7 is not the only casein derived product driving such behavioural impairments. Quantitative autoradiography revealed the casein induced depressive phenotype was concomitant with changes to oxytocin and opioid receptors in regions of the brain associated with mood. Fluorescence in situ hybridization showed an increase in Clostridium Histolyticum in the gut suggesting a microbiome-gut-brain axis role in the casein induced changes reported. In line with this, antibiotic knock-down of gut microbial activity not only prevented the development of the casein induced depressive phenotype, but also caused a casein independent antidepressive-like effect as assessed by the FST. Lastly, metabonomic analysis revealed an increase in gut microbial metabolites and disruptions to choline and energy metabolism in response to prolonged casein exposure, which have been implicated in mood disorders. Collectively, these findings suggest casein exposure beyond weaning age results in neurochemical and emotional impairments via a potential microbiome-gut-brain axis mechanism. This indicates that prolonged breastfeeding periods may cause mood disorders in humans and highlight the need for more comprehensive guidelines regarding an appropriate weaning age."

    Coffee contains potent opiate receptor binding activity (read: can potentially ANTAGONIZE exorphins)
    https://www.nature.com/articles/301246a0

    "Opiate receptor-active peptide fragments (exorphins) have been identified recently in casein1 and gluten2 hydrolysates, and morphine has been found in bovine and human milk3. To determine whether similar peptides or alkaloids occur in other foodstuffs, we have screened potential sources using a rat brain homogenate assay to detect opiate receptor activity. We report here that instant coffee powders from a variety of manufacturers compete with tiitiated naloxone for binding to opiate receptors in the rat brain membrane preparations, with no significant difference between normal and decaffeinated coffee. The receptor binding activity resembles that seen with opiate antagonists, in that there was no change in the half-maximal effective dose (ED50) in the presence of 100 mM Na+; on bioassay, the activity was similarly shown to be antagonistic and specific for opiate-induced inhibition of twitch. "

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    Replies
    1. Aspie, This might explain why in the beginning when I was using the ketogenic classic diet with heavy casein there were changes in my son over time where he was having trouble with his mood, he was sluggish, and he began to grab me and he started using a great deal of non-verbal communication instead of verbal communication. He regressed at age 3 later went on the keto diet. During the regression he retained some speech but it was non-conversational. The ketogenic diet helped him get off of the AED's from seizures but the heavy use of casein had a further impact on his speech and mood. Eliminating casein helped regain the non-conversational speech baseline and I later realized that some in moderation is ok but not heavy amounts.

      Delete
  6. 4-Caffeoyl-1,5-quinide in roasted coffee inhibits [3H]naloxone binding and reverses anti-nociceptive effects of morphine in mice.
    https://www.ncbi.nlm.nih.gov/pubmed/15088081

    "These results suggest that the previously reported anti-opioid activity of instant coffee is caused primarily by the presence of 4-CQL, and to lesser extent by other cinnamoyl-1,5-quinides."


    Might be worth adding (hard pherhaps, as kids often dont like the taste of coffee) decaff coffee/decaff instant coffee?

    FYI: I still believe I fit into the 'malfunctioning proper opioid functioning' subtype of ASD aswell, for instance I have completely eliminated any form of regular milk and gluten in my diet for the last 2-3 years. And yes brewed coffee infact is one of the only thing that helps with my anhedonia/apathy, stuff like ritalin and other dopaminergics dont even come close to having this effect highlighting the potential anti-opioid effect in this.

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  7. Gut bacteria have been coevolving with the people of pastoral cultures for a very long time. Also, for people who are lactose intolerant, milk might make them gassy or nauseous, but they won't instantly become autistic. It is an interesting hypothesis nevertheless. Autism tracks with reduced gut diversity, so the loss of species in the microbiome that may process proteins like casein or other proteins in a special way would also support your hypothesis. Personally, I think the gluten and casein evidence with respect to autism at this time is pretty weak.

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  8. On a side note, I once started thinking (as I sometimes do, looking for solutions) - what are they doing about autism in Cuba? So i looked it up. There was not much in medical terms, but they have a very interesting approach to schooling. Kids with development issues all go to special schools, but the kicker is that they all have a teacher each. This stems from something my husband explained to me, as he once went to visit Cuba in a political mission: in Cuba, you finish the schooling you want and the government simply employs you - which means that sometimes there are more waiters than tables in a restaurant, but everybody has a job. So they have no lack of teachers and this was their solution. Not bad.

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  9. What if the laser only destroys neurons?

    This could be useful even so, but we must be cautious.

    ReplyDelete
    Replies
    1. Sunlight can destroy neurons as well if they were to be exposed directly for long enough, especially since much of sunlight is actually in the frequency range of infrared, as are these lasers.

      In terms of tissue damage, it is mostly about total cumulative exposure and that is a function of the power output of the laser and the duration that the tissue is exposed. So-called cold lasers are called "cold" because they don't put out anywhere near the intensity of energy as lasers you might find used for industrial purposes.

      Delete
  10. I still don't understand exactly how KCC2 function is related to CREB. Or, how Bumetanide is related to pathways ending at CREB.
    Anyone?

    It would be useful to know if it does anything to say serotonin/PKA/ERb/mitochondrial pathways, because then I would better know what other interventions I could skip/add.

    /Ling

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  11. Hi everyone,

    Hope everyone is well and I can’t believe we are less than a week away from Christmas. I can assure you that the elves are working especially hard this year…

    I wanted to share a couple of recent papers that I found particularly interesting:

    1. Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder

    http://science.sciencemag.org/content/362/6420/eaat6576

    2. A placental mammal‐specific microRNA cluster acts as a natural brake for sociability in mice

    http://embor.embopress.org/content/early/2018/12/13/embr.201846429

    Both papers have to do with mutations in the non-coding region of our DNA, which accounts for about 98% of our genome.

    In fact, what I find really interesting about the regulatory elements in our “dark genome” is that they can affect hundreds or even thousands of genes, which makes me wonder if this may explain (at least in some cases of ASD) why some ASD kids have such a broad and seemingly unrelated list of symptoms (e.g. GI, immune system, etc.).

    Hope the community finds the above papers of interest!

    AJ

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    Replies
    1. What are the factors promoting de novo mutations in non-coding regions of our DNA?

      This was suspected by a dr. in my son's condition and I agree with the suspicion ....... their are reasons that contributed to these mutations.....that have yet to be disclosed...

      Delete
    2. Hi Never Give Up,

      As you know, De Novo mutations are those that do not exist in either parent, yet appear in their child. My daughter has a De Novo mutation in a coding region (and maybe also in the non-coding region, but we haven't gotten results yet from a whole genome sequencing effort).

      Mutations happen all the time, and I don't know if we'll ever know why a particular mutation occurred, we just have to figure out how to address it.

      I believe that, on average, each person has ~40 de novo mutations, and if one is lucky, they occur in a place where they are not deleterious.

      As I'm sure you know, our DNA is made up of ~3 billion base pairs, some of them comprising protein coding genes and the remainder comprising the non protein-coding region (i.e. the "dark genome"). The protein-coding regions make up only about 1.5% of our genome, while the rest (~98.5%) is the non-coding region.

      Mutations can happen anywhere in our DNA, and since the non-coding region represents such a large part of our genome, I would imagine mutations are more likely to occur there by virtue of the number of base pairs in the non-coding region relative to protein-coding.

      I personally believe that a sizeable number of ASD kids for whom genetic tests didn't turn up anything do have a de novo mutation in the non-coding region, but that the test done just didn't pick it up. There are several research efforts now underway to identify such mutations in the non-coding region.

      Now, in your case, you say that this was suspected by a dr. in your son's case. May I ask what kind of genetic testing you had done (assuming you have done any genetic testing)?

      There are a few different types, there is "whole genome" sequencing where the entire genome is sequenced, and this includes coding and non-coding regions.

      There is "whole exome" sequencing where only the protein coding regions are sequenced.

      There are other variants, for example we only did sequencing of ~2,500 known ASD genes, but I am now seeking a whole genome sequencing as well as I want to ensure that we know of any other relevant mutations.

      Best regards,

      AJ

      Delete
  12. Hi Ling!

    Hope all is well and that you're ready for Christmas!

    Ling, I wanted to ask you a few questions about the genetic test you had done. Would you kindly connect with me at aj.brookes@yahoo.com ?

    Thanks Ling!

    AJ

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  13. Hi Peter,

    Whilst on the subject of left of field Autism treatment approaches. I was wondering if you could give your opinion on the legitimacy of this device.

    https://www.mentetech.com

    It has all the hallmarks of a scam/snake oil, however the company share price went through the roof last year on the back of announcements that a clinical trial had yielded outstanding results.

    I have become a little less suspicious recently when the published results came back earlier this year.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041407/

    I still think it’s a bit too good to be real but as an ASD parent I always live in hope.




    ReplyDelete
    Replies
    1. Hi Kei,

      The ATEC assessment tool was developed by ARI (the people behind DAN! Doctors) because they felt trials missed actual improvements in autism.

      Based on this assessment the device does not look effective.

      “The autism treatment evaluation checklist (ATEC)
      Statistically significant results were found in both groups but with different directions of the effects for the single scales: For the Active group, the behavior worsened for the Speech and the Sensory/Cognitive Awareness whereas the Sociability improved. For the Control group, only the Health/Physical Behavior showed a statistically significant improvement No statistically significant results were found with the reference to the Total score.”

      I also noted that of the 41 that had the actual treatment, 22 did not bother to show up for the assessment afterwards. That suggests to me that they were not overly impressed by the effect.

      This does not mean that this device does not work wonders in a small group, perhaps it does.

      The results of the LLLT trial were much more impressive, in my opinion, but can they be replicated?

      Delete
  14. Hi Peter,

    Thanks for looking into that. I knew I smelled a rat somewhere. Like you said maybe it does work, but for $AU3000- you want more than a maybe.

    In regards to LLLT my daughter’s Neurologist is in Cuba right now. I’ll ask I f he knows the Drs mentioned in the trials. I can’t imagine the Neurologist community in Cuba is particularly large.

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  15. https://diaryofrecovery.com/2024/01/18/redlight/

    ReplyDelete
  16. I started lllt device for my son. Initially he was improving so good that he has less brain fog, good motor skills, good condition but after 3weeks he got a flare of ear infection and then he spiralled back to the state. I am still doing it to see how things going on. Samething happened after stem cells. I can report later

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